{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:29:43Z","timestamp":1788877783480,"version":"build-2803163510"},"reference-count":116,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Single-cell RNA sequencing (scRNA-seq) enables high-resolution profiling of immune heterogeneity. Although previous studies have mapped the single-cell transcriptomic atlases of peripheral leukocytes in healthy dogs, the identification and functional characterization of distinct immune subsets remain incomplete.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We constructed a single-cell atlas of peripheral leukocytes from six healthy small-breed dogs using the 10x Genomics platform and the updated canFam4 genome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      Analysis of 30,040 high-quality transcriptomes revealed 51 distinct immune subsets, including\n                      <jats:italic>CD14<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      <jats:italic>CD33<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      monocytes,\n                      <jats:italic>XCR1<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      <jats:italic>CD1D<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      dendritic cells,\n                      <jats:italic>CEACAM1<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      <jats:italic>CD24<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils, and\n                      <jats:italic>IL32<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      <jats:italic>BATF<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      regulatory T cells, which were underrepresented in canFam3.1-based studies. Interferon-enriched\n                      <jats:italic>CD14<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      monocytes and\n                      <jats:italic>CD4<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      T subsets associated with myxomatous mitral valve disease were also identified. Functional enrichment analyses suggested that\n                      <jats:italic>PDCD1<\/jats:italic>\n                      is associated with attenuated TCR signaling, whereas\n                      <jats:italic>LAG3<\/jats:italic>\n                      was associated with malate metabolism pathways in\n                      <jats:italic>CD4<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      T cells and reduced\n                      <jats:italic>TBX21<\/jats:italic>\n                      expression in\n                      <jats:italic>CD8<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      T cells linked to antiviral responses.\n                      <jats:italic>CD274<\/jats:italic>\n                      , which encodes PD-L1 was linked to IL-10 production in neutrophils, and\n                      <jats:italic>CTLA4<\/jats:italic>\n                      represented an initial activation of double-negative T subsets. T cell exhaustion scores and proliferative fractions varied across cohorts, reflecting differences in environmental antigenic exposures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>To our knowledge, this study represents the first comprehensive, gene-resolved single-cell analysis to reveal immunoregulatory checkpoint mechanisms underlying immune homeostasis in healthy dogs. Our dataset will serve as a valuable resource for future comparative and translational immunology research in dogs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1680437","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:44:53Z","timestamp":1766040293000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["High-resolution single-cell RNA sequencing using canFam4 reveals novel immune subsets and checkpoint programs in healthy 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